This project aims at proving or disproving the transmethylation hypothesis in mental disease. A sensitive method has been developed for the quantitation of 5-methoxytryptamine in tissues. Preliminary experiments demonstrate that this substance occurs in the CNS of some species but not in that of others. Additional studies will attempt to localize this substance in other parts of the body and may demonstrate its functional role in the organism. By use of mass fragmentography in the chemical ionization mode the technique can be further refined and will hopefully allow the quantitation of other psychoactive methylated indoles such as 5-methoxy-N, N-dimethyltryptamine. In collaboration controlled clinical studies will be performed in order to determine the role of methylated indoles in mental disease. The influence of psychopharmacological agents and other drugs will also be studied.